Elucidating the factors responsible for regulating the T cell response in health and disease has led to important insights into the mechanics of the immune response as well as exciting clinical applications. CD2, or T11, is a 50 kilodalton glycoprotein felt to be important in both helper and cytolytic T cell activities. While much information has been gathered regarding its function in vitro, its physiologic significance remains poorly understood. In particular, its role in T cell activation in vivo as well as its influence on thymic ontogeny is unclear. One of the classic approaches to study the function of a particular gene is to delete or mutate the gene and then examine the subsequent effects. With the availability of the techniques of gene targeting and blastocyst mediated transgenesis, the technology now exists to generate a mouse model of CD2 deficiency. A CD2 deficient mouse offers the possibility to test the hypothesis that CD2 is necessary for the normal maturation of T cells in the thymus. Furthermore it has been speculated that CD2 enhances but is not required for T cell activation through the CD3-T cell receptor complex in vivo. A mouse lacking CD2 would be a valuable tool in examining this theory by assessing the function of CD2 negative T cells in the normal physiologic state. Studies of the immune response in mice have proved crucial in advancing our knowledge of the human immune system and it is anticipated that studies of murine CD2 function will lead to greater insight into human CD2 function as well.